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Nano Research

Article Title

Entrapping multifunctional dendritic nanoparticles into a hydrogel for local therapeutic delivery and synergetic immunochemotherapy

Authors

Lei Jiang, State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009,. China MOE Key Laboratory of High Performance Polymer Materials and Technology, and Department of Polymer Science & Engineering, College of Chemistry & Chemical Engineering, Nanjing University, Nanjing 210093, China
Yang Ding, State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009,. China
Xialin Xue, State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009,. China
Sensen Zhou, MOE Key Laboratory of High Performance Polymer Materials and Technology, and Department of Polymer Science & Engineering, College of Chemistry & Chemical Engineering, Nanjing University, Nanjing 210093, China
Cheng Li, MOE Key Laboratory of High Performance Polymer Materials and Technology, and Department of Polymer Science & Engineering, College of Chemistry & Chemical Engineering, Nanjing University, Nanjing 210093, China
Xiaoke Zhang, MOE Key Laboratory of High Performance Polymer Materials and Technology, and Department of Polymer Science & Engineering, College of Chemistry & Chemical Engineering, Nanjing University, Nanjing 210093, China
Xiqun Jiang, MOE Key Laboratory of High Performance Polymer Materials and Technology, and Department of Polymer Science & Engineering, College of Chemistry & Chemical Engineering, Nanjing University, Nanjing 210093, China

Keywords

multifunctional dendritic nanoparticles, peptide dendrimer, cancer therapy, combined chemotherapy and immunotherapy

Abstract

ABSTRACT Developing multifunctional nanoparticles to support new therapy models is a promising and challenging task to address the current dilemma on antitumor treatment. Herein, we incorporated multifunctional dendritic nanoparticles into a poly(D,L-lactide-co-glycolide)-poly(ethylene glycol)-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers thermosensitive injectable hydrogel matrix to construct a localized drug delivery system for combining chemotherapy and immunotherapy. The multifunctional dendritic nanoparticles were designed with following expectations: i, Dendritic scaffolds provide a hydrophobic interior to load the anticancer drug, doxorubicin (DOX), for chemotherapy; and ii, dendritic scaffolds are used to build arginine-rich molecules to provide the inducible nitric oxide synthase (iNOS) substrate, L-Arg, to M1 macrophages, which can produce the cytotoxic substance nitric oxide (NO) and subsequently induce tumor cell destruction through immunotherapy. It is noteworthy that the dendritic nanoparticles-in-hydrogel delivery system is able to gel at physiological temperature and serves as a warehouse for the sustained release of the drug. Ultimately, this system showed great efficacy in treating 4T1 cells-xenografted BALB/C mice (86.62% tumor growth inhibition). Therefore, this localized drug delivery system combining chemotherapy and immunotherapy provides a novel approach for cancer therapy.

Graphical Abstract

Publisher

Tsinghua University Press

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